Experiments are directed toward understanding processes by which the immune system is regulated at the cellular level. The integrated pathways of the cascade of regulatory cells such as macrophages, thymus-derived helper and suppressor T-cells, as well as the B-cells are being mapped. We are seeking to understand cell circuitry from the precursor stage through the various phenotypic stages between suppressor and helper functional stages. Our results involving the prerential activation/or inactivation of the suppressor function of T-cells by natural microbial agents such as the streptococcal exotoxin, SPE, have delineated a novel approach towards understanding regulatory pathways and T-cell circuitry in the immune system. We have recently achieved stabilization of several helper T-cell phenotypes as functional T-cell hybridomas. We have progressed also towards establishing cell clones which may express an effector cell (cytotoxic or killer) phenotype. This approach is facilitating the ascertainment of definitive regulatory roles of T-cells. These monoclonal and perpetual T-cell clones also provide stable cellular targets for understanding the mechanisms of interference by microbes, their inhibitors, and their mitogens in immune systems.